目的 报道1个骨骼肌钠通道α1亚基(SCN4A)基因新突变导致的正常钾和低钾性周期性瘫痪家系的临床和病理改变特点.方法 本家系为常染色体显性遗传,共有9例患者,男性4例,女性5例,发病年龄7～25岁.5例患者为正常钾性周期性瘫痪,其中4例伴随肌强直症状;3例患者为低钾性周期性瘫痪;1例发作时血钾浓度不详.对先证者进行左肱二头肌活体组织检查.先证者和7例家系患者、3名无症状家系成员以及50名健康人行SCN4A基因测序.结果 先证者的肌纤维出现轻度肥大和萎缩,伴随核内移和肌纤维内空泡,部分肌纤维内氧化酶分布异常.所有患者均存在SCN4A基因的R1129Q突变,3名无症状家系成员以及50名健康对照无此突变.结论 SCN4A基因R1129Q新突变在同一家系内可以导致低血钾性和正常血钾性周期性瘫痪共存.
Objective To describe the clinical and myopathological phenotype of periodic paralysis in a family associated with a novel mutation in the skeletal muscle sodium channel a subunit (SCN4A) gene.Methods Nine patients in a family presented periodic paralysis in an inheritance pattern of autosomal dominant.Except for 1 deceased patient,3 affected individualshad hypokalemic periodic paralysis and 5 showed normokalemic periodic paralysis.Among the patients with normakalemia,4 had muscle stiffness and myalgia;3 showed myotonia discharges in electromyogram explorations,and 1 had worsened weakness after potassium administration.A muscle biopsy was performed in the proband.SCN4A gene mutation screening was carried out in 8 patients.3 asymptomatic family members and 50 health controls.Results Muscle biopsy indicated vacuolar myopathy with abnormal distribution of oxidative enzyme activity.Genetic analysis revealed novel heterozygous missense mutation G3386A in exon 18 of SCN4A gene.The mutation substituted an arginine for a glutamine at the amino acid site1129(R1129Q).Conclusions Hypokalemic and potassium-sensitive normokalemic periodic paralysis can occur sporadically in different affected family members caused by the novel SCN4A mutation at codon R1129Q.